Physiology and pharmacology of skeletal muscle Flashcards
What does a motor unit consist of?
A nerve branch and all the fibres it innervates
What is the neurotransmitter used in skeletal muscle?
ACh
How is ACh generated?
Choline + acetyl CoA (catalysed by choline acetyltransferase)
How is ACh concentrated in vesicles?
By the vesicular ACh transporter
Describe how the arrival of an action potential at the nerve terminal induces neurotransmitter release.
Opens voltage-gated calcium channels; calcium influx causes fusion of vesicles with membrane and exocytosis of ACh
What kind of receptor is located at the neuromuscular junction?
Nicotinic ACh receptors
How is the end plate potential generated?
ACh binding opens the ACh receptor channel and generates a net depolarization (driven by sodium influx)
What does “one to one coupling” mean in the context of skeletal muscle action potential generation? What does this depend upon?
One action potential in the nerve = one action potential in the muscle. Requires the e.p.p. to have sufficient amplitude to generate depolarization (all or nothing event)
What does the action potential in skeletal muscle trigger?
Release of calcium from the sarcoplasmic reticulum
How is the action of ACh terminated?
Acetylcholinesterase (associated with the post-synaptic membrane) cleaves ACh to form choline (which is taken up again) and acetate (which diffuses away)
What causes neuromyotonia?
Autoantibodies against the voltage activated K+ channels causing repetitive firing (cramps, stiffness, slow relaxation)
How are the following types of myasthenia caused? What is the treatment?
a) Lambert-Eaton
b) Myasthenia gravis
a) antibodies against voltage-gated Ca channels causing decreased ACh release
b) antibodies against nACh receptor causing decreased end plate potential
Treated with anticholinesterases
How does botulinum toxin cause paralysis?
Irreversibly modifies proteins involved in Ach exocytosis (membrane docking)
How do curare compounds cause paralysis?
Competitive antagonism of ACh at nACh receptor
